Menstrual Blood Mesenchymal Stem Cells: Boon in Therapeutics

Review Article | DOI: https://doi.org/10.31579/2766-2314/032

Menstrual Blood Mesenchymal Stem Cells: Boon in Therapeutics

  • K. Pushkala 1
  • PD Gupta 2*

1 Former, Associate Professor, SDNB Vaishnav College for Women, Chennai India.
2 Former, Director Grade Scientist Centre for Cellular and Molecular Biology, Hyderabad, India

*Corresponding Author: PD Gupta. Director Grade Scientist Centre for Cellular and Molecular Biology, Hyderabad, India.

Citation: K. Pushkala and PD Gupta, (2021) Menstrual Blood Mesenchymal Stem Cells: Boon in Therapeutics. J, Biotechnology and Bioprocessing 2(4); DOI: 10.31579/2766-2314/032

Copyright: © 2021, PD Gupta, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 09 March 2021 | Accepted: 05 April 2021 | Published: 08 April 2021

Keywords: stem cells; menstrual blood mesenchymal stem cells; therapeutic efficacy

Abstract

Stem cell therapy gained momentum for the past three decades in therapeutics. Alternative strategies are indispensable for the treatment of many diseases in the present scenario due to side effects of synthetic chemicals as drugs. Mesenchymal cells of different origin have been in use with good results, though ethical issues and limited availability is a drawback. Novel menstrual blood mesenchymal stems cells prove to be a wealth out of waste is a boon in therapeutics. In this review we bring a bird’s eye view of different diseases treated with menstrual blood mesenchymal stem cells with positive results. Evolution in the use of these cells more and more will be a big relief to many who suffer with side effects of drugs.

Introduction

After knowing well that almost every drug has side effect(s), researchers wanted to find a therapeutic procedure where side effects are eliminated. The cell therapy instead, injects, graft or implant compatible viable cells, which effectuates a medicinal effect without any chemical drug. In the present scenario, a flourishing research field, cell-based therapy involves modifications of the patient's own cells or cells from a donor to fight a disease and alleviate medical conditions.

Stem cells Therapy

Cells which are capable of regeneration and differentiation into a wide range of specialized cell types are used for stem cell therapy which are of the following types

  • Foetal stem cells (FSCs).
  • Adult stem cells (ASC).
  • Pluripotent stem cells (PSC).

Stem cells (SC) are immature or undifferentiated cells with the capacity to self-renew, differentiate and repopulate a host in vivo [1]. Remarkable plasticity or potency is hierarchical ranging from totipotent (differentiating into all cell types including placenta), pluripotent (differentiating into cells of the three germ layers, but not trophoblastic cells), multipotent (differentiating into cells of more than one type but not necessarily into all the cells of a given germ layer) to unipotent (differentiating into one type of cell only, e.g.  Muscle or neuron).

FSCs appear to be more primitive and have greater multi-potentiality than their adult counterparts and can be isolated during gestation from many different tissues such as blood, liver and bone marrow as well as from a variety of extra-embryonic tissues such as amniotic fluid and placenta. They have been observed to differ on many biological aspects such as growth kinetics, morphology, immunophenotype, differentiation potential and engraftment capacity in vivo.

Adult stem cells can be found in almost all tissues such as brain, dental pulp, muscle, bone marrow, skin and pancreas with their therapeutic potential. The adult stem cell could be multipotent (e.g. haematopoietic stem cells (HSCs) giving rise to all blood cells and adherent stromal/mesenchymal stem cells (MSCs) that give rise to bone, fat, cartilage and muscle) or unipotent (e.g. progenitor cells). Adult MSCs have the problem of being difficult to extract in sufficient numbers for therapy and/or presenting restricted plasticity and limited proliferative capacity compared with FSCs cells.

Pluripotent stem cells can be derived from the inner cell mass of the pre-implantation embryo (i.e. FSCs cells) or isolated from the foetal primordial germ cell pool (PGC) above the allantois (i.e. embryonic germ (EG) cells and embryonic carcinoma (EC) cells [2, 3]. Induced pluripotent stem cells have unique abilities to self-renew and to recreate functional tissues. The destruction of the blastocyst or early foetus necessary for their derivation/isolation raises ethical concerns [4], although recent work has shown that FSCs cells can be derived from single blastomeres isolated using procedures similar to those routinely used for pre-implantation genetic diagnosis [5, 6]. Stem cells can keep dividing as long as they are alive and they have two important features: they can create other stem cells and/or they can become multiple types of more specialized cells. These cells or their derivatives when transplanted or infused, promote the repair response of diseased, dysfunctional or injured tissues. Nowadays, stem cell therapy has become an effective strategy for SCI (Spinal cord injury) [7, 8]. The most promising stem cells are neural stem cells (NSCs), because of their ability to differentiate into neural and glial cells when transplanted in the site of injury [9]. However, some drawbacks also shadowed with NSCs such as non availability of adult NSCs for autologous cell transplant, and ethical concerns of the foetal-derived NSCs. Clinical trials on the use of bone marrow, hematopoietic (mobilized and recovered in blood and umbilical cord blood) and mesenchymal stem cells are in the pipe line [10].

Mesenchymal stem cells (MSCs)

Within the past several years, MSCs have been explored as vehicles for both cell therapy and gene therapy. MSCs are multipotent adult stem cells which can be differentiated into multiple cell types [11].These cells can be isolated from the bone marrow, umbilical cord blood, adipose tissue, muscle, and dental pulp. Transplantation of MSCs into the injured rat spinal cord promoted tissue preservation by directly replacing the damaged cells, decreasing the cyst and injury area, stimulating axonal sprouting, producing neurotrophic factors, as well as inhibiting inflammatory cytokines. In comparison with NSCs, MSCs show a high degree of genomic stability during culture and typically do not result in tumour formation. Centre for Genomic Regulation (CRG) in Barcelona are developing a stem cell treatment for retinal degeneration by using engineered mesenchymal stem cells (from bone marrow ) to have an excessive amount of Ccr5 and Cxcr6 and transplanted them into models of retinal degeneration which preserved the function of degenerating retinal tissue. Mesenchymal stem cells could offer several advantages for the treatment of eye diseases, including an ability to differentiate into retinal cells and to be grown outside the body. When the altered cells were transplanted into models of human and mouse retinal diseases, the cells migrated in high numbers to deteriorating retinal tissue and prevented the death of retinal cells [12].

Menstrual blood-derived mesenchymal stem cells (MenSCs)

Menstrual blood-derived mesenchymal stem cells (MenSCs) are boon in therapeutics and a list of diseases are treated and more are in pipeline undergoing clinical trials [13] (Fig-1). Approximately a decade ago, Meng et al. and Cui et al. discovered a novel source of MSCs from human menstrual fluid, named menstrual blood-derived stem cells (MenSCs) [14, 15]. These SC have high rate of proliferation and possess multi lineage differentiation potency as well as its differentiation into epidermal lineage is remarkable [16, 17].

Figure 1. Different diseases treated with MenSCs.

MenSCs are giving hopes in clinical application that can be harvested from human menstrual blood shedding of endometrium which is a highly dynamic and a powerful substance. Scientists in Japan have found that cells taken from menstrual blood can be cultured in the laboratory and used like SC, which can even repair damaged heart tissue. Scientists devoted to researching SC, found that the lining of the uterus, which is a main constituent of period blood, have an abundance of these cells. MenSCs proliferate faster than the stem cells from umbilical cord and can be manipulated to transform into all kinds of cells, including those found in fat, muscle, bone, and nerves.

Menstrual fluid consists of blood, extra tissue from the uterine lining, remnants of the unfertilized egg that travelled down the fallopian tube into the uterus during ovulation. Women felt better about their periods after being made aware of the ability to donate menstrual fluid, meaning that MenSCs therapy can be beneficial for donors as well as patients. The average volume of menstrual fluid during a monthly menstrual period is 35 ml (2.4 table spoons of menstrual fluid), with 10–80 ml (1–6 tablespoons of menstrual fluid) considered typical. The blood contains sodium, calcium, phosphate, iron, and chloride, the extent of which depends on the woman. In addition to blood, the fluid consists of cervical mucus, vaginal secretions, and endometrial tissue. Vaginal fluids in menses mainly contribute water, common electrolytes, organ moieties, and at least 14 proteins, including glycoproteins.

With potential for multi-directional differentiation, MenSCs are able to undergo adipogenic, chondrogenic, osteogenic, myogenic and neurogenic differentiation in vitro [18, 19]. Compared with other sources of MSCs, MenSCs can be easily selected in a periodic manner and obtained by a noninvasive method, avoiding the ethical issues [20], do not form teratomas [21], and can be expanded by at least 20 passages without genetic abnormalities [22]. In recent studies, MenSCs showed potential therapeutic applications in a variety of animal disease models,such as stroke[23], type 1 diabetes [24, 25], and myocardial infarction [26] and so on. Co-culture experiments showed that MenSCs restrained the proliferation of LX-2 cells (HSC line) through secretion of paracrine cytokines, including interleukin-6 (IL- 6), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene (GRO), osteoprotegerin (OPG), hepatocyte growth factor (HGF) by promoting hepatocellular regeneration or inducing the apoptosis of stellate cells and antifibrotic function by inducing G0/G1‐phase arrest in stellate cells.

Therapeutic applications of (MenSCs)

  1. Uterine endometriosis

Inactive endometrium contains hormone independent clonogenic epithelial and stromal cells which does not vary from the proliferative to secretory stage of the menstrual cycle, or between active cycling and inactive endometrium for both epithelial and stromal cells [27]. Activation of the Hippo/TAZ pathway is required for menstrual stem cells to suppress myofibroblast and inhibit transforming growth factor β signalling in human endometrial stromal fibrosis [28].

  2. Fulminant hepatic failure

Human menstrual blood-derived stem cells alleviate fulminant hepatic failure (FHF). Parekkadan et al. [29] for the first time have shown that ·Mesenchymal Stem Cell-Derived Molecules (Exosomes) can also reverse FHF in mice in vitro and in vivo.

Figure 2. The origin of microvesicles and exosomes from cells

Microvesicles which arises by budding from the plasma membrane are more irregular in shape and size and can contain cytoplasmic materials. Micro vesicles express surface markers such as integrin-β, CD40 and selectins such as plasma selectins and/or proteins from the cells they originate from. Exosomes originate from the endosomal trafficking system (therefore, are more regular in shape and size), easily identifiable via cell surface markers such as CD81, CD9 and CD63 and may contain materials such as mitochondrial DNAs, mRNAs and miRNAs; microRNA; multi-vesicular bodies (MVB)(Figure 2).

  3. Skin disease

Inflammatory skin disorders resulting in serious deterioration of the quality of life becomes one of the major public concerns. Unfortunately, despite their significance, there is no fundamental cure to date. Only BM (bone marrow) derived MSCs possess unique immunomodulatory properties which make them a promising tool for the treatment of various inflammatory diseases especially within the skin due to the suppressive effect on T cell proliferation till today. MSCs from menstrual blood can be successfully used for the treatment of atopic dermatitis (AD), dermatitis, and psoriasis. In addition, it has been proposed that cell priming or gene transduction can be novel strategies for the development of next-generation high-efficacy MSCs for treating inflammatory skin diseases [30].

  4. Premature ovarian failure (POF)

The incidence of premature ovarian failure (POF) has been increasing in recent years. Many researchers have reported that MenMSCs, were tracked in ovarian tissues within 2 months after transplantation, and they differentiated into granulosa cells (GCs). Therefore, the use of these cells can be a practical and low-cost method for the treatment of POF patients. Several studies have shown that MenMSCs, reduce apoptosis in granulosa cells and fibrosis of the ovarian interstitium, thereby improving folliculogenesis and rescuing overall ovarian function in an animal model of POF [31], including restoring fertility [32]. In addition, Wang et al. demonstrated that MenMSCs, produced a high level of fibroblast growth factor 2, which enhanced cell survival, proliferation, and function to repair tissue damage [33], hence, we can safely conclude that the mesenchymal stem cells and in vivo survival of MenMSCs, make them ideal seed cells for stem cell transplantation in the treatment of POF.

  5. Ischemic stroke

Transplantation of MenSCs, (either intracerebrally or intravenously and without immune suppression), after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused animals. MenSCs exemplify a source of “individually tailored” donor cells that completely match the transplant recipient, at least in women. Autologous menstrual-blood-derived cells previously collected, expanded up to third passage and cryopreserved would still benefit from the use of allogeneic cells which, being stromal cells, present low immunogenicity and, therefore, tolerable rejection rates [34, 35].

  6. Critical Limb ischemia

De novo angiogenesis based on MenSCs therapy is considered as a promising treatment for acute limb ischemia. MenSCs significantly improved hind limb ischemia. The recovery of the ischemic tissue returned to normal in mice. These results indicate that menstrual blood is a promising source to isolate stem cells for hind limb ischemia treatment [36, 37].

  7. Duchenne muscular dystrophy

Umezawa’s team [38, 39] successfully transdifferentiated MenSCs into myoblasts/myocyts in vitro and restored sarcolemmal expression of dystrophin in dystrophied muscle of Duchennemuscular dystrophy (DMD) in mice. Cellularfusion between adipocytes and dystrophied myocytes expressed dystrophin [40] providing positive results for the treatment of Duchenne muscular dystrophy.

  8. Alzheimer's disease

Intracerebral transplantation of MenSCs dramatically improved the spatial learning and memory of APP/PS1 mice as well as significantly ameliorated amyloid plaques and reduced tau hyperphosphorylation in APP/PS1 Alzheimer's disease in mouse model. MenSCs markedly increased several Aβ (amyloid-beta) degrading and anti-inflammatory impact of MenSCs in the brains of APP/PS1 mice. Similar results could be anticipated in humans also by clinical trials which are yet to be done [13, 41].

  9. Myocardial infarction

Transplanted MenSCs significantly restored the damaged cardiac function, reduced apoptosis, promote cell proliferation, and stimulate angiogenesis which rescued the myocardium in the infarct region, and recruited c-kit + cells. Expression of some specific cytokines to activate AKT/extracellular signal-regulated kinases 1 and 2 (ERK 1/2)/signal transducers and activator of transcription 3 (STAT 3) and suppress p38 signaling pathway also was noticed [42, 43], Wang’s team found that MenSCs inhibited endothelial cell to mesenchymal transition (EMT), which helped to reduce the total number of cardiac fibroblasts and tissue fibrosis progression [44]. The secreted exosomes of miR-21 mediated and enhanced the paracrine and cytoprotective effects through a transwell co-culture system in vitro. MenSCs transplantation decreased fibrosis area and restored the LV systolic function in the MI (myocardial infarction) model in vivo. Engrafted MenSCs are trans-differentiated into cardiomyocyte within MI area. MenSCs can be a major cell source for stem cell therapy to achieve cardiomyogenesis.

  10. Diabetes

Intravenous injection of human menstrual blood progenitor cells (MBPCs) can reverse hyperglycemia and weight loss, prolong lifespan, and increase insulin production in diabetic mice. Histological and immunohistochemistry analysis indicated that T1DM mice with MBPCs transplantation recovered islet structures and increased the β-cell number. In vivo distribution of MBPCs when analysed a majority of MBPCs migrated into damaged pancreas and located at the islet, duct, and exocrine tissue. MBPCs did not differentiate into insulin- producing cells, but enhanced neurogenin 3 (ngn3) expression, which represented endocrine progenitors that were activated. Ngn3+ cells were not only in the ductal epithelium, but also in the islet and exocrine tissue. MenSCs could facilitate β-cell regeneration and enhance the number of β cells by increasing the expressions of neurogenin 3 (ngn 3), forkhead box A2 (foxa 2), pancreatic and duodenal homeobox 1 (pdx 1), NK homeobox factor 6.1 (nkx 6.1), and paired box gene (pax) to activate endogenous progenitor cell differentiation in MenSCs transplantation in T1DM mice. [45].The levels of these gene expressions all increased after cell transplantation.

  11. HSC Liver Fibrosis

Liver function was improved by MenSCs via targeting activated hepatic stellate cells (HSCs). MenSCs significantly reduced collagen deposition and improved liver function within 2 weeks of transplantation in a mouse model. These stem cells underwent hepatocyte differentiation based on CK‐18 expression. Moreover, during the tracking of green fluorescent protein-expressing MenSCs demonstrated that transplanted cells migrated to the sites of injury, but few differentiated into functional hepatocyte-like cells. Results provide preliminary evidence for the antifibrotic capacity of MenSCs in liver fibrosis [46, 47, and 48].

  12. Acute lung injury

MenSCs promoted the repair of injured lung by inhibiting the inflammatory response in LPS (lipopolysaccharide)-induced ALI acute lung injury in mice [49]. Furthermore, MenSCs not only improved pulmonary microvascular permeability, reduced histopathological injury, down regulated the expressions of IL-1β and caspase-3, up regulated the levels of IL-10 in bronchoalveolar lavage fluid (BALF) in the damaged lung, proliferating cell nuclear antigen (PCNA), and keratinocyte growth factor (KGF) in bronchoalveolar lavage fluid (BALF). MenSCs could also increase the survival rate of BEAS-2B cells (human normal lung epithelial cells) [50].

  13. Asherman syndrome

Asherman's syndrome is an uncommon, acquired, gynaecological disorder characterized by changes in the menstrual cycle caused by the formation of adhesions in the uterine cavity. Patients experience reduced menstrual flow, increased cramping and abdominal pain, eventual cessation of menstrual cycles (amenorrhea), and, in many instances, infertility, (including amenorrhea, less menstruation, or dysmenorrhea), and repeated pregnancy loss [51]. This can be treated by autologous MenSCs transplantation that significantly increased endometrial thickness (ET) in Asherman syndrome women in 7 patients [52]. They showed that the ET of 5 women was significantly increased to 7 mm (a thickness to ensure embryo implantation). Four of these patients were subjected to frozen embryo transfer (FET). Surprisingly, one patient developed a spontaneous pregnancy only after the second MenSCs transplant.

  14. Epithelial ovarian cancer

Epithelial ovarian cancer develops from the cells that cover the outer surface of the ovary. Most epithelial ovarian tumors are benign (noncancerous). EOC has been found to be advanced in most cases, with a combination of extensive abdominal metastasis, high recurrence, and chemo resistance [53]. This benign tumour can be treated successfully with MenSCs due to its intrinsic anti-tumor properties. EOC cells in vivo and in vitro provide a strategy for MenSCs -based anti-cancer therapy against epithelial ovarian cancer [54-56].

Conclusion

To conclude more research and clinical trials with menstrual blood mesenchymal stem cells therapy will pave way to solve many problems in treating patients. Development of sophisticated culturing and harvesting technologies to genetically engineer need based stem cells will be a breakthrough MenSCs in therapeutics.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad